Prediction of Chronic Kidney Disease Stage 3 by CKD273, a Urinary Proteomic Biomarker.

Kleins Lab // Publications // Nov 01 2017

PubMed ID: 29130072

Author(s): Pontillo C, Zhang ZY, Schanstra JP, Jacobs L, Zürbig P, Thijs L, Ramírez-Torres A, Heerspink HJL, Lindhardt M, Klein R, Orchard T, Porta M, Bilous RW, Charturvedi N, Rossing P, Vlahou A, Schepers E, Glorieux G, Mullen W, Delles C, Verhamme P, Vanholder R, Staessen JA, Mischak H, Jankowski J. Prediction of chronic kidney disease stage 3 by CKD273, a urinary proteomic biomarker. Kidney Int Rep. 2017 Nov;2(6):1066-1075. doi: 10.1016/j.ekir.2017.06.004. PMID 29130072

Journal: Kidney International Reports, Volume 2, Issue 6, Nov 2017

INTRODUCTION CKD273 is a urinary biomarker, which in advanced chronic kidney disease predicts further deterioration. We investigated whether CKD273 can also predict a decline of estimated glomerular filtration rate (eGFR) to <60 ml/min per 1.73 m2.

METHODS In analyses of 2087 individuals from 6 cohorts (46.4% women; 73.5% with diabetes; mean age, 46.1 years; eGFR ≥ 60 ml/min per 1.73 m2, 100%; urinary albumin excretion rate [UAE] ≥20 μg/min, 6.2%), we accounted for cohort, sex, age, mean arterial pressure, diabetes, and eGFR at baseline and expressed associations per 1-SD increment in urinary biomarkers.

RESULTS Over 5 (median) follow-up visits, eGFR decreased more with higher baseline CKD273 than UAE (1.64 vs. 0.82 ml/min per 1.73 m2; P < 0.0001). Over 4.6 years (median), 390 participants experienced a first renal endpoint (eGFR decrease by ≥10 to <60 ml/min per 1.73 m2), and 172 experienced an endpoint sustained over follow-up. The risk of a first and sustained renal endpoint increased with UAE (hazard ratio ≥ 1.23; P ≤ 0.043) and CKD273 (≥ 1.20; P ≤ 0.031). UAE (≥20 μg/min) and CKD273 (≥0.154) thresholds yielded sensitivities of 30% and 33% and specificities of 82% and 83% (P ≤ 0.0001 for difference between UAE and CKD273 in proportion of correctly classified individuals). As continuous markers, CKD273 (P = 0.039), but not UAE (P = 0.065), increased the integrated discrimination improvement, while both UAE and CKD273 improved the net reclassification index (P ≤ 0.0003), except for UAE per threshold (P = 0.086).

DISCUSSION In conclusion, while accounting for baseline eGFR, albuminuria, and covariables, CKD273 adds to the prediction of stage 3 chronic kidney disease, at which point intervention remains an achievable therapeutic target.